Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells.

ABSTRACT:

Background

Ewing's sarcoma is a childhood bone and soft tissue cancer with poor prognosis. Treatment outcomes for Ewing's sarcoma patients have improved only modestly over the past decades, making the development of new treatment strategies paramount. In this study, the combined targeting of ribonucleotide reductase (RNR) and WEE1 was explored for its effectiveness against Ewing's sarcoma cells.

Methods

The RNR inhibitor triapine and the WEE1 inhibitors adavosertib and ZN-c3 were tested in p53 wild-type and p53 mutant Ewing's sarcoma cells. The combination of adavosertib with the PARP inhibitors olaparib and veliparib was tested for comparison. Combinatorial effects were determined by flow cytometric analyses of cell death, loss of mitochondrial membrane potential and DNA fr

SUBMITTER: Ziener J 

PROVIDER: S-EPMC11831844 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature